Dr. Xiaoyu Zhang, Agilent Technologies
January 19, 2022
Understanding drug-mediated modulation of cardiac contractility is an important question from both a therapeutic angle and a safety/toxicity angle. Even though human iPSC-derived cardiomyocytes (hiPSC-CMs) have been validated as a suitable model for assessment of contraction (Scott C. et al, 2013), their fetal-like phenotypes, such as immature contractile apparatus and the calcium handling mechanisms have hampered full utilization. To address this limitation, we developed a multi-modal connected workflow to evaluate the effect of inotropic compounds in electrically paced human iPSC-derived cardiomyocytes (hiPSC-CMs) through calcium imaging. The workflow is instituted using the electrical pacing feature of the Agilent xCELLigence RTCA ePacer to achieve functional maturation of hiPSC cardiomyocytes. Once functional maturity of the cells has been achieved, based on a positive force-frequency relationship (FFR), inotropic compounds are added to the cells. The cellular responses to inotropes are monitored by fast-kinetic measurement of Ca2+ transient on the Hamamatsu FDSS/µCELL system. Our data demonstrate that the workflow provides higher translatable results to assess the modulation of cardiomyocyte contractility by inotropic compounds. It uses a physiologically relevant readout for screening of efficacious inotropes in addition to the assessment of potential liability of pharmaceutical drugs.
Dr. Zhang is covering the role of Senior Research Scientist for the xCELLigence RTCA platform at Agilent Technologies. She is specialized in the development of applications for xCELLigence RTCA Cardio-related instruments, leading cardiac safety screening programs. Her research has led to multiple publications in peer-reviewed journals. Also, she provides technical support for RTCA Cardio-related systems through training, workshops, and webinars. Dr. Zhang attained her Ph.D. in Cell Molecular and Development Biology from the University of California, Riverside, and received postdoctoral training at Sanford Burnham Prebys Medical Discovery Institute.
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